This invention relates to the preparation of L-aspartic acid N-thiocarboxyanhydride, which is a useful intermediate for the synthesis of peptides. In particular, L-aspartic acid N-thiocarboxyanhydride is useful for reaction with L-phenylalanine lower alkyl esters to form L-aspartyl-L-phenylalanine lower alkyl esters, which are useful as potent sweetening agents for use in food stuffs and beverages. The methyl ester is especially preferred as a sweetening agent.
The preparation of amino acid N-thiocarboxyanhydride derivatives is described in J. Org. Chem. 36, 49 (1971). One method of interest is by the reaction of an N-alkoxythiocarbonyl amino acid with a phosphorous trihalide. In order to allow the use of L-aspartic acid N-thiocarboxyanhydride as an intermediate for the preparation of L-aspartyl-L-phenylalanine lower alkyl esters for use in food products, it is necessary to be able to prepare the L-aspartic acid N-thiocarboxyhydride in good yields and in high purity.